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BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma

Digestive Diseases and Sciences volume 62, pages 3501–3510 (2017)Cite this article

Abstract

Background

Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear.

Aims

To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells.

Methods

BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo.

Results

BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo.

Conclusions

BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81472261), the Natural Science Foundation of Guangdong Province (No. 2015A030313032), the Science and Technology Development Projects of Guangdong Province, China (No. 2013B021800122), the Science and Technology Development Projects of Guangzhou, Guangdong, China (No. 201604020044).

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Author notes

  1. Chen-Song Huang and Jing-Ming Zhai have contributed equally to this work.

Authors and Affiliations

  1. Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Chen-Song Huang, Xiao-Xu Zhu, Jian-Peng Cai, Wei Chen, Jian-Hui Li & Xiao-Yu Yin

  2. Department of General Surgery, The First Affiliated Hospital, Henan Science and Technology University, Luoyang, 471000, China

    Jing-Ming Zhai

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  1. Chen-Song Huang
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  2. Jing-Ming Zhai
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  4. Jian-Peng Cai
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  5. Wei Chen
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  6. Jian-Hui Li
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Correspondence to Xiao-Yu Yin.

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Huang, CS., Zhai, JM., Zhu, XX. et al. BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma. Dig Dis Sci 62, 3501–3510 (2017). https://doi.org/10.1007/s10620-017-4829-y

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Keywords

  • B cell translocation gene 2
  • Side population cells
  • Hepatocellular carcinoma
  • Cancer stem cell